Brain Activity and Functional Connectivity Patterns Associated With Fast and Slow Motor Sequence Learning in Late Middle Adulthood

The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning [i.e., fast learning (FL)]. A subset of these subjects (n = 11) was evaluated after extensive practice of a motor sequence [i.e., slow learning (SL) phase]. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs.

Skill reconsolidation does not operate at a rapid micro-timescale level

Abundant evidence shows that consolidated memories are susceptible to modifications following their reactivation through reconsolidation. Processes of memory consolidation and reconsolidation have been commonly documented after hours or days. Motivated by studies showing rapid consolidation in early stages of skill acquisition, here we asked whether skill memories are susceptible to modifications through rapid reconsolidation, even at initial stages of learning. In a set of experiments, we collected crowdsourced online motor sequence data to test whether post-reactivation interference and enhancement occur through rapid reconsolidation. Results indicate that memories forming during early learning are not susceptible to interference nor to enhancement within a rapid reconsolidation time window, relative to control conditions. This set of evidence suggests that memory reconsolidation might be dependent on consolidation at the macro-timescale level, requiring hours or days to occur.

Extracting temporal relationships between weakly coupled peptidergic and motoneuronal signaling: Application to Drosophila ecdysis behavior

Neuromodulators, such as neuropeptides, can regulate and reconfigure neural circuits to alter their output, affecting in this way animal physiology and behavior. The interplay between the activity of neuronal circuits, their modulation by neuropeptides, and the resulting behavior, is still poorly understood. Here, we present a quantitative framework to study the relationships between the temporal pattern of activity of peptidergic neurons and of motoneurons during Drosophila ecdysis behavior, a highly stereotyped motor sequence that is critical for insect growth. We analyzed, in the time and frequency domains, simultaneous intracellular calcium recordings of peptidergic CCAP (crustacean cardioactive peptide) neurons and motoneurons obtained from isolated central nervous systems throughout fictive ecdysis behavior induced ex vivo by Ecdysis triggering hormone. We found that the activity of both neuronal populations is tightly coupled in a cross-frequency manner, suggesting that CCAP neurons modulate the frequency of motoneuron firing. To explore this idea further, we used a probabilistic logistic model to show that calcium dynamics in CCAP neurons can predict the oscillation of motoneurons, both in a simple model and in a conductance-base model capable of simulating many features of the observed neural dynamics. Finally, we developed an algorithm to quantify the motor behavior observed in videos of pupal ecdysis, and compared their features to the patterns of neuronal calcium activity recorded ex vivo. We found that the motor activity of the intact animal is more regular than the motoneuronal activity recorded from ex vivo preparations during fictive ecdysis behavior; the analysis of the patterns of movement also allowed us to identify a new post-ecdysis phase.

Offline low-frequency rTMS of the primary and premotor cortices does not impact motor sequence memory consolidation despite modulation of corticospinal excitability

Motor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to either low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of left dPMC, rTMS of left M1, or sham rTMS. rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess potential stimulation-induced changes in corticospinal excitability (CSE). Participants were retested on motor sequence performance after eight hours to assess consolidation. While rTMS of dPMC significantly increased CSE and rTMS of M1 significantly decreased CSE, no CSE modulation was induced by sham rTMS. However, all groups demonstrated similar significant offline learning indicating that consolidation was not modulated by the post-training low-frequency rTMS intervention despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by low-frequency rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE.

Black-box testing in motor sequence learning

During learning of novel motor sequences, practice leads to the consolidation of hierarchical structures, namely motor chunks, facilitating the accurate execution of sequences at increasing speeds. Recent studies show that such hierarchical structures are largely represented upstream of the primary motor cortex in the motor network, suggesting their function to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We isolated different components of motor skill acquisition related to the consolidation of spatiotemporal features and followed their evolution over training. We found that optimal motor skill acquisition relies on the storage of the spatial features of the sequence in memory, followed by the optimization of its execution and increased execution speeds (i.e., a shift in the speed-accuracy trade-off) early in training, supporting the model proposed by Hikosaka in 1999. Contrasting the dynamics of these components during ageing, we identified less-than-optimal mechanisms in older adults explaining the observed differences in performance. We applied noninvasive brain stimulation in an attempt to support the aging brain to compensate for these deficits. The present study found that anodal direct current stimulation applied over the motor cortex restored the mechanisms involved in the consolidation of spatial features, without directly affecting the speed of execution of the sequence. This led older adults to sharply improve their accuracy, resulting in an earlier yet gradual emergence of motor chunks. The results suggest the early storage of the sequence in memory, largely independent of motor practice, is crucial for an optimal motor acquisition and retrieval of this motor behavior. Nevertheless, the consolidation of optimal temporal patterns, detected as motor chunks at a behavioral level, is not a direct consequence of storing the sequence elements, but rather of motor practice.

Additive and interaction effects of working memory and motor sequence training on brain functional connectivity

Although shared behavioral and neural mechanisms between working memory (WM) and motor sequence learning (MSL) have been suggested, the additive and interactive effects of training have not been studied. This study aimed at investigating changes in brain functional connectivity (FC) induced by sequential (WM + MSL and MSL + WM) and combined (WM × MSL) training programs. 54 healthy subjects (27 women; mean age: 30.2 ± 8.6 years) allocated to three training groups underwent twenty-four 40-min training sessions over 6 weeks and four cognitive assessments including functional MRI. A double-baseline approach was applied to account for practice effects. Test performances were compared using linear mixed-effects models and t-tests. Resting state fMRI data were analysed using FSL. Processing speed, verbal WM and manual dexterity increased following training in all groups. MSL + WM training led to additive effects in processing speed and verbal WM. Increased FC was found after training in a network including the right angular gyrus, left superior temporal sulcus, right superior parietal gyrus, bilateral middle temporal gyri and left precentral gyrus. No difference in FC was found between double baselines. Results indicate distinct patterns of resting state FC modulation related to sequential and combined WM and MSL training suggesting a relevance of the order of training performance. These observations could provide new insight for the planning of effective training/rehabilitation.

Regular rhythmic and audio-visual stimulations enhance procedural learning of a perceptual-motor sequence in healthy adults: A pilot study

Procedural learning is essential for the effortless execution of many everyday life activities. However, little is known about the conditions influencing the acquisition of procedural skills. The literature suggests that sensory environment may influence the acquisition of perceptual-motor sequences, as tested by a Serial Reaction Time Task. In the current study, we investigated the effects of auditory stimulations on procedural learning of a visuo-motor sequence. Given that the literature shows that regular rhythmic auditory rhythm and multisensory stimulations improve motor speed, we expected to improve procedural learning (reaction times and errors) with repeated practice with auditory stimulations presented either simultaneously with visual stimulations or with a regular tempo, compared to control conditions (e.g., with irregular tempo). Our results suggest that both congruent audio-visual stimulations and regular rhythmic auditory stimulations promote procedural perceptual-motor learning. On the contrary, auditory stimulations with irregular or very quick tempo alter learning. We discuss how regular rhythmic multisensory stimulations may improve procedural learning with respect of a multisensory rhythmic integration process.

Effects of sleep on language and motor consolidation: Evidence of domain general and specific mechanisms

The current study explores the effects of time and sleep on the consolidation of a novel language learning task containing both item-specific knowledge and the extraction of grammatical regularities. We also compare consolidation effects in language and motor sequence learning tasks, to ask whether consolidation mechanisms are domain general. Young adults learned to apply plural inflections to novel words based on morpho-phonological rules embedded in the input and learned to type a motor sequence using a keyboard. Participants were randomly assigned into one of two groups, practicing each task during the morning or evening hours. Both groups were retested 12 and 24 hrs. post training. Performance on frequent trained items in the language task stabilized only following sleep, consistent with a hippocampal mechanism for item-specific learning. However, regularity extraction, indicated by generalization to untrained items in the linguistic task, as well as performance on motor sequence learning, improved 24 hours post training, irrespective of the timing of sleep. This consolidation process is consistent with a fronto-striatal skill learning mechanism, common across the language and motor domains. This conclusion is further reinforced by cross domain correlations at the individual level between improvement across 24 hours in the motor task and in the low-frequency trained items in the linguistic task, which involve regularity extraction. Taken together, our results at the group and individual levels suggest that some aspects of consolidation are shared across the motor and language domains, and more specifically between motor sequence learning and grammar learning.

EFFECT OF ACTION OBSERVATION THERAPY ON IMPROVING UPPER LIMB FUNCTIONS IN ACUTE STROKE PATIENTS: AN EXPERIMENTAL STUDY

BACKGROUND & PURPOSE: The most common disabling motor decit following stroke is the loss of upper limb function. 5-20% of patients presenting an upper limb paralysis at onset may improve the motor impairment overtime. Action observation training is a novel rehabilitation approach exploiting this mirror mechanism and its potential role in motor learning for motor recovery. Aim of this study was to examine the effects of action observation therapy on upper limb functions in acute stroke patients. METHODOLOGY: Stroke survivors (N= 50) were consecutively recruited 22 days (±5) after a rst-ever stroke and participants watched video footage of daily routine tasks (actions). Each action based on some relevant ADLs motor sequence display in order of ascending difculty and lasting for 3 minutes and therapist prompted the patient to perform the same movement for 2 minutes. At the end of each sequence, patients were given conventional physiotherapy and AOT 1 hour daily for 5 days/week for 4 weeks. RESULTS: Upper Limb part of FMA, Modied Ashworth Scale scores & nine-hole peg test were taken at baseline and after 4 weeks as outcome measure. Paired 't' test and Wilcoxon's signed-rank has been used for analysis of Fugl Meyer scale, Modied Ashwarth Scale and Nine-hole peg pre and post treatment scores respectively (p value<0.05) So, a statistically signicant difference was found after treatment for all variables. CONCLUSION: The nding of this study is suggesting that Action observation training programs contribute to improve motor recovery in acute stroke patients.